Our findings showed that when compared with other genotypes, individuals carrying the genotype CC of NRG1 had lower Type A behavior. This was true with total Type A and its trait-related subscale.
The trait-related subscale differentiated the genotypes whereas the job-related subscale did not. This would be in line with an assumption that trait-related Type A behavior is more innate and job-related behavior more circumstantial. It should be noted that calculating the total Type A behavior in the way used, also emphasizes the portion of trait-related Type A compared to job-related Type A behavior.
As the etiology of Type A is still unclear, an association between NRG1 and Type A behavior might provide hints of the physiological basis of this personality type and imply a mechanism through which Type A behavior may have its effect on health. NRG1 plays a part in the survival, growth and repair of adult cardiomyocytes as a response to increased workload [16
]. It is also crucial in the development of the autonomic nervous system [16
] and the heart [17
]. Therefore some autonomic or cardiostructural function of NRG1 could be related to Type A. One intriguing possibility for explaining the association is the adrenergic system. Type A behavior has been associated with increased sympathetic balance compared to parasympathetic tone [10
]. It has been linked, in particular, to the beta-adrenergic system in men, as it has been associated with greater B2 adrenergic receptor density [8
], and in a more recent study to greater sensitivity to B1 and B2 receptor agonist isoproterenol administered by bolus injection [9
]. In Type A men, isoproterenol has a stronger effect on the T wave of the cardioelectrogram, and parasympathetic antagonism of beta-adrenergic stimulation also appears to be less effective [10
Neuregulin proteins, on their part, appear to have the ability to control excessive beta-adrenergic activation. This is, incidentally, likely to be a key factor in neuregulin's protective role in heart failure [6
]. In animal studies, neuregulin-1 has been shown to induce counterbalancing parasympathetic activity [7
] and to directly reduce contractibility in heart muscle cells [6
]. Thus, adrenergic responses might play a role in the etiology of Type A and would be an interesting focus of further molecular research.
It has primarily been through responses to stressors that Type A has been thought to be pathogenic, even when considered as risk factor for atherosclerosis [19
] and not just a trigger for coronary events. If Type A behavior is, indeed, an actual risk factor for atherosclerosis, neuregulin could be involved in additional ways. As mentioned above, neuregulin has a protective role in heart failure. In rat cardiomyocytes, neuregulin-1 activates endothelial nitric oxide synthase [6
], and there is evidence that the nitric oxide synthase has a role in both heart failure and atherosclerosis [20
]. Although neuregulin proteins are beneficial in heart failure, they may, in fact, play a pathological role in atherosclerosis.
Neuregulin has been found to be overexpressed in coronary atherosclerotic lesions in the intima of human blood vessels, primarily in macrophages [11
]. Type A, in turn, has been associated with coronary atherosclerosis in Sparagon's study with male subjects [22
] and also with markers of arteriosclerosis [23
]. The different NRG1 genotypes might, therefore, mark variation in both susceptibility to Type A and the development of atherosclerosis. This hypothesis must, however, be considered with caution, as the link between different NRG1 forms and atherosclerotic factors has not yet been thoroughly investigated.